Migraine And Psychiatric Disease
Headache and psychiatric disorders have many links and parallels in their classification, diagnosis, comorbidity, mechanisms, and treatment. Silberstein et al. (1995) reviewed a number of studies that examined the relationship of migraine to specific psychiatric disorders. Several clinic-based studies have reported an increased prevalence of migraine in patients with major depression and an increased prevalence of major depression in patients with migraine (Marchesi et al., 1989; Merikangas et al., 1988; Morrison and Price, 1989). Three population-based studies have examined a wide range of psychiatric disorders in addition to major depression (Breslau et al., 1991; Merikangas, 1990, 1993; Stewart et al., 1989, 1992).
Merikangas et al. (1990) reported on the association of migraine with specific psychiatric disorders in a random sample of 457 adults between 27 and 28 years of age in Zurich, Switzerland. Persons with migraine (n = 61) were found to have increased 1-year rates of affective and anxiety disorders. Specifically, the OR for major depression (OR = 2.2, 95% CI 1.1 – 4.8), bipolar spectrum disorders (OR = 2.9, 95% CI 1.1 – 8.6), generalized anxiety disorder (OR = 2.7, 95% CI 1.5 – 5.1), panic disorder (OR = 3.3, 95% CI 0.8 – 13.8), simple phobia (OR = 2.4, 95% CI 1.1 – 5.1), and socihobia (OR = 3.4, 95% CI 1.1 – 10.9) were significantly higher in persons with migraine than in persons without migraine.
Migraine with major depression is frequently complicated by an anxiety disorder. In persons with all three disorders, Merikangas et al. (1990) suggest that the onset of anxiety generally precedes the onset of migraine, whereas the onset of major depression usually follows the onset of migraine (Silberstein et al., 1995).
Stewart et al. (1989) studied the relationship of migraine to panic disorder and panic attacks in a population-based telephone interview survey of 10,000 residents of Washington County, Maryland, who were between the ages of 12 and 29. The highest rates of migraine headaches occurring in the preceding week were reported by men and women with a history of panic disorder. The RR of migraine headache occurring during the previous week and associated with a history of panic disorder was 6.96 in men and 3.70 in women.
In a follow-up analysis of the same sample, Stewart et al. (1992) found that 14.2% of women and 5.8% of men who had experienced headache in the previous 12 months had consulted a physician for the problem. An unexpectedly high proportion of those who had consulted a physician for headache had a history of panic disorder. Of those who had recently seen a physician, 15% of women and 12.8% of men between 24 and 29 years of age had a panic disorder. This suggests that comorbid psychiatric disease is associated with seeking care for headache disorders.
Breslau et al. (1991) studied the association of IHS-defined migraine with specific psychiatric disorders in a sample of 1,007 young adults between 21 and 30 years of age in southeast Michigan. Persons with a history of migraine (n = 128) had significantly higher lifetime rates of affective disorder, anxiety disorder, illicit drug disorder, and nicotine dependence. Sex-adjusted ORs were 4.5 (95% CI 3.0 – 6.9) for major depression, 6.0 (95% CI 2.0 – 18.0) for manic episode, 3.2 (95% CI 2.2 – 4.6) for any anxiety disorder, and 6.6 (95% CI 3.2 – 13.9) for panic disorder (Breslau and Davis, 1993). The psychiatric comorbidity odds associated with migraine with aura were generally higher than those associated with migraine without aura (Breslau et al., 1991). Migraine with aura was associated with an increased lifetime prevalence of both suicidal ideation and suicide attempts, after controlling for the factors of sex, major depression, and other concurring psychiatric disorders (Breslau, 1992).
Using follow-up data gathered 3.5 years after baseline, Breslau et al. (1994a) reported on the prospective relationship between migraine and major depression in a cohort of young adults. The RR for the first onset of major depression during the follow-up period in persons with prior migraine vs. those with no prior migraine was 4.1 (95% CI 2.2 – 7.4). The RR for the first onset of migraine during the follow-up period in persons with prior major depression vs. those with no history of major depression was 3.3 (95% CI 1.6 – 6.6).
In summary, recent epidemiologic studies support the association between migraine and major depression previously reported in clinic-based studies. The prospective data indicate that the observed cross-sectional or lifetime association between migraine and major depression could result from a bidirectional influence, from migraine to subsequent onset of major depression and from major depression to first migraine attack. Furthermore, these epidemiologic studies indicate that persons with migraine have increased prevalence of bipolar disorder, panic disorder, and one or more anxiety disorders (Silberstein et al., 1995; Breslau and Davis, 1992; Breslau et al., 1994a, b).
Major depression in persons with migraine might represent a psychologic reaction to repeated, disabling migraine attacks. Migraine has an earlier mean age at onset than major depression, both in the general population and in persons with comorbid disease. Nonetheless, the bidirectional influence of each condition on the risk for the onset of the other is incompatible with the simple causal model (Breslau et al., 1994a, b, 2000). Furthermore, Breslau and Davis (1992) reported that the increased risk for a first episode of major depression (and/or panic disorder) did not vary by the proximity of migraine attacks. These findings lessen the plausibility that the migraine-depression association results from the demoralizing experience of recurrent and disabling headaches, suggesting instead that their association might reflect shared etiologies.
Breslau et al. (2000) examined the migraine-depression comorbidity in a largescale epidemiologic study, the Detroit Area Study of Headache. The study comprised three groups: persons with migraine (n = 536), persons with other severe headaches of comparable pain severity and disability (n = 162), and matched controls with no history of severe headache (n = 586). These three representative samples of the population were identified by a random-digit dialing telephone survey of 4,765 persons 25 to 55 years of age.
The lifetime prevalence of major depression was 40.7% in persons with migraine, 35.8% in those with other severe headaches, and 16.0% in controls. Sex-adjusted ORs in the two headache groups, relative to controls, were approximately of the same magnitude, 3.5 and 3.2. However, examination of the bidirectional relationship between major depression and each headache type yielded different results. A bidirectional relationship was observed with respect to migraine: migraine signaled an increased risk for the first onset of major depression and major depression signaled an increased risk for the first occurrence of migraine.
Sex-adjusted hazard ratios were 2.4 and 2.8, respectively (both statistically significant). In contrast, severe nonmigraine headache signaled an increased risk for major depression, but there was no evidence of a significant influence in the reverse direction, i.e., from major depression to severe headache. Sex-adjusted hazard ratios were 3.6 and 1.6, respectively (only the first statistically significant).
The pattern of the results suggests that different causal pathways might account for the comorbidity of major depression in these two headache categories. The results for migraine suggest shared causes, whereas those for other headache of comparable severity suggest a causal effect of headache on depression.
Another line of evidence comes from a study of a biologic marker of depression in migraineurs. Jarman et al. (1990) administered the tyramine test to 40 migraine patients, 16 of whom had a lifetime history of major depression. Low tyramine conjugation, a trait marker for endogenous depression, was strongly associated with a lifetime history of major depression in subjects with comorbid disease, regardless of their current psychiatric status. The authors argued that the association of the trait marker with major depression in migraineurs ruled out the possibility that the depression was a psychologic reaction to migraine attacks (Silberstein et al., 1995).
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Aaron L Shechter
Richard B Lipton
Stephen D Silberstein
Editors: Silberstein, Stephen D.; Lipton, Richard B.; Dalessio, Donald J.